Session Information
Date: Tuesday, November 10, 2015
Title: Rheumatoid Arthritis - Clinical Aspects IV: Biomarkers, Disease Progression and Treatment Response
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Rheumatoid arthritis (RA) is characterized by joint inflammation and destruction of cartilage and bone. The destructive process is related to autoantibodies, genetic polymorphisms involving proteins in the Wingless related MMTV integration site (Wnt) pathway and markers of inflammation, cartilage and bone. We have analysed the relationships of receptor activator of nuclear factor kappa-B ligand (RANKL) and sclerostin to radiological destruction and progression in early RA.
Methods: Patients with early RA (n=414, symptom duration <1 year) (ARA criteria) with radiological examinations at inclusion and after 24 months were consecutively included. Disease activity score, swollen (SJC) and tender (TJC) joint count, ESR, CRP and treatment were regularly registered. Concentrations of sclerostin (EIA, TECOmedical group, Sissach, Switzerland), RANKL (ELISA, BioVendor, Karasek, Czech Republic) and anti-CCP2 antibodies (ELISA, Euro-Diagnostica AB, Malmö, Sweden) were analysed at baseline. Data on gene polymorphisms were extracted from Immunochip analysis (Uppsala, Sweden).
Results: RANKL concentration was significantly higher in patients compared with controls (p <0.001). Anti-CCP positive patients had significantly higher concentration of RANKL compared with anti-CCP negatives, median (Q1-Q3) 763.7 (347.3-1325.0) pmol/L and 241.5 (137.8-474.1) pmol/L. Sclerostin was significantly increased in patients 0.63 (0.49-0.78) ng/mL versus controls (0.51 (0.4-0.7) ng/mL (p <0.01). After stratification for sex the difference was only significant in females, 0.59 (0.47-0.74) ng/mL compared with controls.
RANKL concentration was related to Larsen score at baseline (p<0.01), and after 24 months (p<0.001) and to radiological progression after 24 months (p<0.001). After adjustments (age and SJC), RANKL was only related to Larsen score at baseline. Sclerostin was significantly (p< 0.05) related to radiological progression after 24 months adjusted for sex, Larsen score and ESR at baseline and 24 months’ treatment response.
The less frequent type of three SNPs (rs41848320, rs41887440, rs41931102) encoding RANKL was associated with increased concentrations, particularly in the RA-patients, although unrelated to radiological findings. The levels of sclerostin were not related to any of the SNPs.
Conclusion: The concentration of RANKL was related to Larsen score at baseline, whilst the concentration of sclerostin was related to radiological progression during the first 2 years. Measurement of sclerostin at baseline could be a valuable predictor of radiological progression during the first 2 years. Polymorphisms of three SNPs showed increased concentrations of RANKL but were unrelated to radiological findings.
To cite this abstract in AMA style:
Boman A, Kokkonen H, Berglin E, Ärlestig L, Rantapaa-Dahlqvist S. Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Sclerostin Are Related to Joint Destruction in Early Rheumatoid Arthritis Unrelated to Polymorphisms of the Genes [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/receptor-activator-of-nuclear-factor-kappa-b-ligand-rankl-and-sclerostin-are-related-to-joint-destruction-in-early-rheumatoid-arthritis-unrelated-to-polymorphisms-of-the-genes/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/receptor-activator-of-nuclear-factor-kappa-b-ligand-rankl-and-sclerostin-are-related-to-joint-destruction-in-early-rheumatoid-arthritis-unrelated-to-polymorphisms-of-the-genes/